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In the clinical diagnosis of breast cancer, immunohistochemistry panels with estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and Ki-67 are routinely used, and they have been proposed for the classification of breast tumors into distinct subtypes. Gene expression analysis with formalin-fixed paraffin-embedded material have also become widely available recently, but the prognostic values of corresponding gene panels compared with these four immunohistochemical panels had never tested. We independently evaluated the 5-year relapse risk-estimation scores using semiquantitative data of four immunohistochemical panels (Ku-IHC4 score) and compared these with the results of four-gene expression profiling of formalin-fixed paraffin-embedded specimens (Ku-FFPE4 score) in a consecutive series of 235 primary invasive breast cancer patients. Ku-IHC4 score was revealed to be an independent predictor of recurrence other than Ku-FFPE4 score in a multivariate model analyzed by classical clinical parameters (Ku-IHC4 score vs Ku-FFPE4 score; χ(2): 14.2 vs 2.5, P: 0.0002 vs 0.11). When patients were trichotomized into high-, intermediate- and low-risk groups using the thresholds determined from the approximately calculated 5-year relapse rate, Kaplan-Meier analyses showed a significant difference among the three groups in Ku-IHC4 score (log-rank, P<0.0001), but not in Ku-FFPE4 score. The high-risk group according to Ku-FFPE4 score showed contradictory low recurrence rates (Ku-IHC4 score vs Ku-FFPE4 score, 53.1 vs 24.8%), which might be caused by risk-dependently extended error ranges. We show that the Ku-IHC4 score, consisted with semiquantitative measures of immunohistochemistry, provides better prognostic information than the corresponding quantitative RNA measurements. Prognostication tools such as the Ku-IHC4 score may be potentially useful in screening which patients had better be assessed by further testing using other genes rather than ER, PgR, HER2 and Ki-67 to determine critical aspects of therapeutic decision making.

Primary malignant melanoma of the esophagus (PMME) is an exceedingly rare tumor. The prognosis of PMME is very poor, and the 5-year survival rate is only 2.2% due to its aggressive biologic character. We present patient with PMME with wide extension into almost the entire esophagus, without endoscopic abnormalities. This patient's presentation is extremely valuable because it has enabled us to observe the long-term natural progression of PMME, including recurrent disease with a wide range of atypical melanocytic cells in the entire esophagus., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Breast elastography (EG), which can objectively evaluate tumor stiffness, has been useful for differentiation of benign and malignant breast lesions. However, the value of EG for prediction of response to systemic therapy is poorly understood., Methods: The baseline evaluations of EG in 55 patients who received neoadjuvant chemotherapy were reviewed. We investigated the correlation between tumor stiffness and response to neoadjuvant chemotherapy. Tumor stiffness was evaluated by the Tsukuba elasticity scoring system., Results: The mean EG scores were significant lower for the clinical and pathologic complete response (pCR) groups than for the others. When we categorized patients into two groups according to tumor stiffness, 26 patients were assigned to the low EG group (soft, scores from 1 to 3) and 29 patients were assigned to the high EG group (hard, score 4 and 5). The low EG group had significantly higher clinical complete response and pCR rates than the high EG group (clinical complete response, low EG group 38 % vs. high EG group 10 %, P = 0.024; pCR, low EG group 50 % vs. high EG group 14 %, P = 0.003, respectively). Furthermore, multivariate analysis indicated that estrogen receptor, human epidermal growth factor receptor 2, and low EG (odds ratio 13.04, 95 % confidence interval 1.19-458.28, P = 0.035) were independent predictive factors of pCR., Conclusions: Tumor stiffness evaluated by EG bears predictive potential for response to neoadjuvant chemotherapy. Stiffness evaluated by EG may be recognized as a clinically significant tumor characteristic, comparable to other data obtained by functional imaging techniques.

CD138 expression is a hallmark of plasma cells and multiple myeloma cells. However, decreased expression of CD138 is frequently observed in plasma cells of myeloma patients, although the clinical significance of this is unclear. To evaluate the significance of low expression of CD138 in MM, we examined the phenotypes of MM cells expressing low levels of CD138. Flow cytometric analysis of primary MM cells revealed a significant decrease in CD138 expression in patients with relapsed/progressive disease compared with untreated MM patients. Patients with low levels of CD138 had a worse overall survival compared with patients with high levels of CD138, in newly diagnosed patients and patients receiving high-dose chemotherapy followed by autologous stem-cell transplantation. Two MM cell lines, KYMM-1 (CD138- low) and KYMM-2 (CD138- high), were established from a single MM patient with decreased CD138 expression. High expression of BCL6 and PAX5, and downregulation of IRF4, PRDM1 and XBP1 was observed in KYMM-1 compared with KYMM-2 cells, indicative of the immature phenotype of KYMM-1. KYMM-1 was less sensitive to lenalidomide than KYMM-2, while no difference in sensitivity to bortezomib was observed. KYMM-2 cells were further divided in CD138+ and CD138- fractions using anti-CD138-coated magnetic beads. CD138- cells sorted from the KYMM-2 cell line also showed high BCL6, low IRF4 expression and decreased sensitivity to lenalidomide compared with CD138+ cells. Our observations suggest that low CD138 expression relates to i) poor prognosis, ii) immature phenotype and iii) low sensitivity to lenalidomide. The observed distinct characteristics of CD138 low MM cells, suggest this should be recognized as a new clinical entity. Establishment of a treatment strategy for MM cells expressing low levels of CD138 is needed to improve their poor outcome.

Meningiomas are the most frequent intracranial tumors. Although most are benign WHO grade I tumors, grade II and III tumors are aggressive and survival is poor. Treatment options for grade II and III meningiomas are limited, and molecular targets are few. The re-programming of metabolic pathways including glycolysis, lipogenesis, and nucleotide synthesis is a hallmark of the physiological changes in cancer cells. Because fatty acid synthase (FAS), the enzyme responsible for the de-novo synthesis of fatty acids, has emerged as a potential therapeutic target for several cancers, we investigated its involvement in meningiomas. We subjected 92 paraffin-embedded samples from 57 patients with grade I, 18 with grade II and III, and six with radiation-induced tumors to immunohistochemical study of FAS. Whereas its expression was increased in grade II and III meningiomas (62.9 %) compared with grade I tumors (29.8 %) (chi-squared test: p < 0.001), FAS was expressed in grade I tumors with a high MIB-1 index and infiltration into surrounded tissues. All radiation-induced meningiomas expressed FAS and its expression was positively correlated with the MIB-1 index (p < 0.005). Our findings suggest that increased FAS expression reflects the aggressiveness of meningiomas and that it may be a novel therapeutic target for treatment of unresectable or malignant tumors.

Disseminated carcinomatosis of the bone marrow derived from solid cancer has a very poor prognosis, with disseminated intravascular coagulation(DIC). A 72-year-old man was admitted to our hospital after detection of a tumor in the pancreatic tail by CT imaging. Several images revealed that he suffered from cancer of the tail of the pancreas with multiple liver and bone metastases. Endoscopic ultra-sonography-guided fine needle aspiration detected adenocarcinoma cells from the tumor of the pancreatic tail. We also performed bone marrow aspiration, which confirmed adenocarcinoma cells in the bone marrow. We started to administer 1,000 mg/m2 of gemcitabine weekly. Laboratory data revealed that thrombocytopenia had occurred, and it developed into DIC after the first the administration of gemcitabine. In spite of the DIC state with thrombocytopenia, we were able to provide anticancer treatment using combination gemcitabine and S-1. He recovered from his DIC state, and the primary tumor was shrunk with a decrease of tumor markers after 2 courses of combination chemotherapy. Chemotherapy might be required for disseminated carcinomatosis of the bone marrow in order to promote tumor shrinkage and to prolonged expected survival, even if DIC was developed.

Background: The mechanisms of IPMN carcinogenesis are as yet unclear. This study aimed to determine whether expression of EZH2 promotes neoplastic progression of IPMN and PDCA, and to elucidate regulation of EZH2 expression by miR-101., Methods: EZH2 mRNA and protein expression were investigated in 8 human pancreatic cancer cell lines by PCR and western blotting. Pre-miR-101 and anti-miR-101 were transfected into pancreatic cancer cells to elucidate EZH2 regulation by miR-101. To evaluate whether EZH2 modulates malignant progression of IPMN, EZH2 expression in IPMN was examined by immunohistochemistry. Next, we collected malignant and benign cells from FFPE samples of IPMNs using laser capture microdissection and extracted the RNA. miR-101 expression in IPMN was assessed using real-time PCR., Results: All pancreatic cancer cell lines expressed EZH2 mRNA and protein. The induction of miR-101 by transfection of pre-miR-101 in MIA PaCa-2 was closely related to a reduction in EZH2 protein production compared with control, whereas there was little difference in the expression of EZH2 mRNA. Anti-miR-101 transfected pancreatic cancer cells showed an increase in EZH2 protein, while the level of EZH2 mRNA was not elevated. Immunohistochemistry revealed that the expression of EZH2 was significantly higher in malignant than benign IPMN. Expression of miR-101 was significantly lower in malignant IPMN than benign IPMN., Conclusions: MiR-101 targets EZH2 at the posttranscriptional level, and loss of miR-101 could be a trigger for the adenomacarcinoma sequence of IPMN by upregulation of EZH2. This study suggests miR-101-EZH2 blockade as a potential therapeutic target in IPMN carcinogenesis.

Background: To examine whether segmentectomy is radical for cT1N0M0 non-small cell lung cancer (NSCLC), a prospective single-arm study was performed at a single institution., Methods: The criteria for segmentectomy were as follows: (1) peripheral-type cT1N0M0 NSCLC; (2) intraoperative frozen sections of sentinel nodes identified with isotope showing no metastasis; (3) surgical margins greater than 2 cm; (4) patient choice for segmentectomy; and (5) exclusion of right middle lobe tumors. From 2005 to 2009, of 245 patients with cT1N0M0 NSCLC, 195 (80%) were enrolled in the present study. Of these 195 patients, 179 ultimately underwent segmentectomy with systematic lymph node dissection. Of these 179 patients, 134 (75%) had tumors 2 cm or smaller, and 45 (25%) had tumors 2.1 cm to 3 cm. The median follow-up period was 43 months., Results: All 181 tumors from 179 patients were stage pN0. Of the 179 patients, 6 developed distant site recurrence and 3 local recurrence (ie, 1 developed pulmonary metastases within the same lobe 21 months after segmentectomy and 2 developed local recurrence at the surgical margin 60 and 62 months after segmentectomy, respectively). The 5-year overall survival was 94% for patients with tumors 2 cm or smaller and 81% for those with 2.1-cm to 3-cm tumors. Postoperative pulmonary function was preserved at 90% ± 12% of preoperative levels., Conclusions: Segmentectomy with systematic lymph node dissection with a sufficient surgical margin could be a radical treatment for selected cT1N0M0/pN0 NSCLC while preserving pulmonary function. The surgical margin should be monitored for the development of local recurrence for a long period after segmentectomy., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background and Objectives: D2-40 staining has been reported to be useful for both identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) in various cancers. The aim of this study was to clarify the prognostic significance of D2-40 staining in patients with esophageal squamous cell carcinoma (ESCC)., Methods: A total of 159 consecutive patients with ESCC who underwent an esophagectomy with lymph node dissection were eligible. LVI was diagnosed by both hematoxylin-eosin (LVI-HE) and D2-40 staining (LVI-D2-40) in the largest central sections of the entire tumors, while both the intratumoral and peritumoral LVD were counted by D2-40 staining. The correlation between the prognosis and clinicopathological factors was investigated., Results: An univariate analysis revealed that tumor invasion beyond the muscularis propria, lymph node metastasis (LNM), LVI-HE, LVI-D2-40, high intratumoral LVD, and blood vessel invasion correlated with worse patients' prognosis (P < 0.05). A multivariate analysis revealed LNM to be the only independent prognostic factor in all cases (P = 0.0083). On the other hand, when the prognostic factors of 83 patients without LNM were investigated, LVI-D2-40 was revealed to be the only independent prognostic factor (P = 0.048)., Conclusions: LVI detected by D2-40 staining was an independent prognostic factor in patients with node-negative ESCC., (Copyright © 2011 Wiley Periodicals, Inc.)

We report a rare case which had been followed up for hepatic hemangioma and in whom was surgical resection revealed with cholangiolocellular carcinoma (CoCC) combined with intrahepatic cholangiocarcinoma (ICC). A 69-year-old man who was an HBV carrier had been regularly followed up with hepatic hemangioma from November, 2005. Because the arterial phase of dynamic CT scan exhibited an enhanced lesion in the dorsal portion of the hemangioma on November, 2009, the patient was admitted for intensive examination of the liver tumor. After surgical resection of the tumor, histological examination revealed small irregular tubules in the outer part and scattered small duct structures in the inner part of the tumor. In addition, immunohistochemical analysis demonstrated that cytokeratin (CK) 7, CK19 and epithelial membrane antigen (EMA) were all positive in the outer part, and EMA was only negative in the inner part of the tumor. From these findings, this case was diagnosed as CoCC combined with ICC.

Skeletal complications represent major clinical problems in multiple myeloma (MM). MM cells are known to induce differentiation of osteoclasts and inhibit osteoblasts. Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) are key molecules for osteoclastogenesis. Although OPG interacts with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), the contribution of TRAIL to skeletal-related events (SRE) remains a matter of debate. In the present study, we examined the role of TRAIL in MM bone lesions. Myeloma cells were purified from 56 MM patients by CD138-immunomagnetic beads. TRAIL, DKK-1 and MIP1α RNA expression in purified MM cells was analyzed by real-time PCR. Immunohistochemistry of TRAIL was performed on paraffin-embedded plasmacytoma tissue sections. The concentration of TRAIL in the serum and bone marrow plasma from MM patients was analyzed by ELISA. TRAIL expression was significantly higher in MM cells than in plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS). TRAIL staining was detected in the cytoplasm of myeloma cells. TRAIL expression in MM cells correlated with bone marrow plasma TRAIL concentration. TRAIL expression had a positive correlation with osteolytic markers, such as serum calcium and urinary deoxypyridinoline. These results suggest that TRAIL, produced from myeloma cells, may play an important role in bone resorption of MM patients. Inhibition of this pathway may lead to development of a new therapeutic approach preventing bone resorption in MM.

Solid-pseudopapillary tumors of the pancreas (SPTs) are comparatively rare and have low malignancy, with a predilection for young women. Diagnosis is difficult when a SPT develops in a boundary region with other organs. Here, we report a 42-year old woman with a SPT of the pancreas mimicking a submucosal tumor of the stomach on imaging. She was admitted to our hospital complaining of abdominal pain. We suspected a submucosal tumor of the stomach from the findings of endoscopy, endoscopic ultrasonography and abdominal computed tomography. However, angiography showed that some of the tumor vessels arose from the pancreas. Intraoperative findings revealed the tumor originated from the pancreas. Therefore, distal pancreatectomy was performed. The pathological diagnosis was SPT of the pancreas.

A 52-year-old man presented with a pulmonary bulky mass, fever and cough. Chest CT showed a necrotizing bulky mass 10 cm in diameter in the right lung lower lobe. Transbronchial biopsy and CT-guided biopsy of the tumor and endobronchial ultrasound-guided transbronchial needle aspiration of the right hilar lymph node did not yield a definitive diagnosis, but the histological findings showed necrosis. We performed CT-guided biopsy of the part of the lesion where a high uptake of FDG-PET was observed. The histological diagnosis was diffuse large B-cell lymphoma. The immunohistochemical findings were positive for Epstein-Barr virus (EBV). Because the patient was more than 50 years old and had no underlying diseases, he was given a diagnosis of EBV-positive diffuse large B-cell lymphoma of an elderly patient. The pulmonary manifestation of this disease as a bulky tumor is extremely rare. In spite of the presence of a bulky pulmonary tumor, the EBV-positive diffuse large B-cell lymphoma contained necrotizing tissue, and it was difficult to obtain tissue specimens for histological examination.

We report magnetoresistance of -40%, corresponding to 80% spin polarization, at magnetic field of 0.5 T and 200 K for oleic acid-coated Fe(2.5)Mn(0.5)O(4) nanocrystals (FMO NCs) self-assembled on a SiO(2)/Si substrate by drop casting fabrication. The FMO NCs exhibited spin glass transition around 150 K and nonlinear current-voltage (I-V) characteristics. Fowler-Nordheim plot of the I-V characteristics indicated that electrons tunnel directly barriers between the FMO NCs. Transmission electron microscopy revealed that the FMO NCs are elongated hexagon in shape with size of ∼15 × 20 nm. The FMO NCs self-assembled in two-dimension hexagonal networks of collinear ferromagnetic moments. The [111] easy magnetization axis of each FMO NC was parallel to each other in the hexagonal arrays. Geometrically frustrated lattice of collinear ferromagnetic moments supports both a low and a high intergranular tunneling conductance for the self-assembled FMO NCs without and with magnetic fields, respectively.

Hepatocellular adenoma is a rare, benign neoplasm that is related to the use of contraceptives or androgenic-anabolic steroids. A 51-year-old man with no history of steroid use was found to have a liver tumor. Plain computed tomography showed a high-density tumor that was enhanced in the arterial phase, and the enhancement was prolonged in the delayed phase. Magnetic resonance imaging showed that the tumor was hyperintense on in- and opposed-phase T1-weighted gradient recalled echo images and hyperintense on T1-weighted spin echo images. A partial hepatic resection was performed. A histological examination revealed normal hepatocyte-like tumor cells, composed of abundant dark brown granules of Dubin-Johnson-like pigment, which stained positively for Masson-Fontana stain. The tumor was diagnosed to be a very rare hepatocellular adenoma with the deposition of Dubin-Johnson-like pigment.

We report a case of 57-year-old Japanese woman with an overlap syndrome of both rheumatoid arthritis (RA) and autoimmune hepatitis, who developed multiple skin nodules. An extensive biopsies of the nodules revealed rheumatoid neutrophilic dermatitis, showing panniculitis without vasculitis, combining with granulomatous formation histopathologically. Since cutaneous nodules in patients with RA are very complex, differential diagnosis should be done according to disease activities, medications used, and pathological findings. We suggest that the differences in histopathological findings of cutaneous nodules in patients with RA depend on their immunological conditions based on disease activities including therapeutic effects.

Background: Human T-cell lymphotropic virus type 1 (HTLV-I) causes not only adult T-cell leukemia (ATL) but also HTLV-I associated T-cell bronchioloalveolitis, which is often chronic and subclinical. We have experienced eight HTVL-I carriers with bronchioloalveolar carcinoma, which is known to arise from bronchioloalveolar pneumocytes. This case-control study clarified the risk of bronchioloalveolar carcinoma in HTLV-I carriers., Materials and Methods: During the past four years, 212 lung cancer patients were examined for serum anti-HTLV-I antibody. They underwent surgical treatment for lung cancer at Kumamoto University Hospital. Of these, 8 (4%) were HTLV-I carriers. As controls for this case-control study, we selected 24 HTLV-I negative-lung cancer patients (1:3 case-control ratio) matched for sex, age, and smoking status. The distributions of histological types of lung cancer were compared between the case (HTLV-I positive) and control (HTLV-I negative) groups., Results: Histological types of the 8 HTLV-I carriers were bronchioloalveolar carcinoma in 6 patients and adenocarcinoma with bronchioloalveolar carcinoma component in 2. The prevalence of bronchioloalveolar carcinoma in HTLV-I carriers, 6 of 8 (75%), was significantly higher than the 6 of 24 (25%) in HTLV-I negative patients (p = 0.02). The prevalence of bronchioloalveolar carcinoma or adenocarcinoma with bronchioloalveolar carcinoma component in HTLV-I carriers, 8 of 8 (100%), was also significantly higher than the 13 of 24 (54%) in HTLV-I negative patients (p = 0.02)., Conclusion: HTLV-I might be one risk of bronchioloalveolar carcinoma, probably because of inflammatory and/or immunologic responses involving bronchioloalveolar pneumocytes.

Three young osteosarcoma patients with adenocarcinoma (AD) or atypical adenomatous hyperplasia (AAH) of the lung are reported. A 14-year-old male patient with femoral osteosarcoma had solitary AD (case 1); a 23-year-old female patient with femoral osteosarcoma had AAH and lung metastasis (case 2); and a 17-year-old male patient with humeral osteosarcoma had AD and lung metastasis of osteosarcoma (case 3). They have been the youngest patients with lung cancer or AAH in our hospital. The maximum diameter of each lung tumor on computed tomography (CT) was 0.5, 0.6, and 0.5 cm, respectively. On immunohistochemical analyses, the p53 was positive in both AD and osteosarcoma and negative in both AAH and osteosarcoma. On genomic analyses, p53 mutation was detected in only one osteosarcoma (case 3). Epidermal growth factor receptor (EGFR) mutations, short in-frame deletion in exon 19, and insertion in exon 20 were found in AD, but not in AAH or osteosarcoma. There was no apparent genomic relationship between AD/AAH and osteosarcoma in the young patients in this study. Advances in CT and its applications to osteosarcoma patients as a method of assessing lung metastasis might contribute in large part to the detection of AD/AAH in patients younger than 30.

Ectopic adrenal cortical neoplasms are extremely rare; few involve the central nervous system (CNS). We report a 17-month-old girl with spinal adrenal cortical neoplasms. She was unable to crawl or stand and was irritable at night. Her appearance was asymmetrical; the right side of her face and her lower right leg were enlarged. In addition, she manifested hyperplasia of the thymus, fibrous hyperplasia of the bladder, and hamartoma in the liver. However, all abnormalities were asymptomatic. Magnetic resonance imaging (MRI) revealed well-circumscribed masses within the dura mater at the T12-L1 and L3-L4 level. Histology disclosed that the lesions were composed of sheets and nests of round and polygonal cells with mostly round regular nuclei; eosinophilic to clear cytoplasm was abundant. Immunohistochemically, the tumor cells were strongly positive for inhibin-alpha, positive for synaptophysin and vimentin, and negative for GFAP, EMA, S-100, NSA, and chromogranin A. In addition, the nuclei stained positive for steroidogenic factor 1 (Ad4BP/SF-1), which is involved in adrenal steroidogenesis. This case confirms the occurrence of adrenocortical adenoma in the CNS. We suggest that this tumor should be considered in the differential diagnosis of CNS tumors.

Background: The mammalian target of rapamycin (mTOR) plays central roles in the regulation of cell growth and proliferation by monitoring nutrient availability, cellular energy level, oxygen level, and mitogenic signals. The aberrant activation of mTOR in relation to clinical outcome has been reported in several types of cancers. mTOR is increasingly important as a potential target for anticancer therapy. Nonetheless, a prognostic feature of mTOR activation in esophageal squamous cell carcinoma (ESCC) remains uncertain., Materials and Methods: First, in order to validate phospho-specific mTOR antibody (Ser2448), phosphorylated mTOR (p-mTOR) expression levels in five ESCC cell lines under cultural conditions with or without everolimus (mTOR inhibitor, also known as RAD001) were evaluated by in vitro immunohistochemistry and immunoblotting. Second, we examined p-mTOR expression by immunohistochemistry using 143 resected ESCC specimens. Prognostic significance of p-mTOR expression was examined by Cox regression and Kaplan-Meier analyses., Results: Among 143 patients, 71 (49.7%) were classified into p-mTOR-positive and 72 (50.3%) were classified into p-mTOR-negative. Compared with p-mTOR-negative patients, p-mTOR-positive patients experienced high overall mortality [hazard ratio (HR) 2.44; 95% confidence interval (CI), 1.24-4.83; P = 0.008], which persisted in multivariate analysis (multivariate HR 2.92; 95% CI, 1.48-5.78; P = 0.002). A similar finding was observed for esophageal cancer-specific mortality. p-mTOR expression was not related with any clinical or pathologic variables including age, sex, tumor location, histological grading, operative procedure, T classification (tumor invasion), or lymph-node metastasis., Conclusions: p-mTOR overexpression was independently associated with poor prognosis in ESCC, supporting the potential for mTOR as a therapeutic target for ESCC.

A solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm that mainly occurs in young women. We herein report the case of a small SPT arising from the head of the pancreas in an asymptomatic 32-year-old man, plus a literature review of this tumor. A 32-year-old man was admitted to our department at Kumamoto University Hospital for the evaluation of a pancreatic mass. The tumor had central necrosis, which was poorly perfused on contrast-enhanced computed tomography (CT) and which had a high intensity on T2-weighted magnetic resonance imaging (MRI). Histology revealed the lesion to be a solid pseudopapillary tumor of the pancreas, with the characteristic pseudopapilla formation and central degeneration. However, no capsule formation was observed. The tumor was positive for CD56, CD10, alpha1-antitrypsin, alpha1-antichymotrypsin, beta-catenin, and progesterone receptor. However, the tumor was negative for pancreatic hormones, chromogranin-A, carcinoembryonic antigen, and carbohydrate antigen 19-9. We diagnosed the patient to have an SPT based on these histological findings. Small-sized solid pseudopapillary tumors of the pancreas are being increasingly recognized because of the recent advances in CT and MRI. We should also consider SPT even if it occurs in a male when the tumor contains necrosis-suspected areas which are poorly perfused on contrast-enhanced CT with a high intensity on T2-weighted MRI.

A 33-year-old female patient was referred to our hospital for further examination of an abnormal shadow evident on a chest X-ray film. Chest computed tomography (CT) revealed a solid nodule 1.9 cm in diameter in the hilum of the upper lobe of the left lung. Positron emission tomography showed high 18F-fluorodeoxyglucose accumulation in the nodule with a maximal standardized uptake value of 4.5, which favored a malignant lesion. Diffusion-weighted magnetic resonance imaging (DWI), which shows differences in the diffusion of water molecules and can discriminate between malignant and benign lesions, indicated that the nodule had a minimum apparent diffusion coefficient of 1.7 × 10-3 mm2/sec, which was higher than the cutoff value of 1.1 × 10-3 mm2/sec for discriminating between malignant and benign diseases; i.e., values equal to or lower than 1.1 × 10-3 mm2/sec favor malignant disease. The results of a CT-guided needle biopsy of the nodule favored sclerosing hemangioma. During surgery, the tumor did not appear to be invasive, and lymph node metastasis and dissemination were not apparent. On the basis of gross appearance, location, preoperative histological diagnosis, and DWI findings, the tumor was enucleated from the pulmonary parenchyma. Seven months after surgery, the patient was alive and had no evidence of recurrent disease.

Neoplasms derived from interdigitating dendritic cell are extremely rare. Here we describe a case of a 47-year-old man with interdigitating dendritic cell sarcoma (IDCS) in the ileum. He was admitted to a hospital due to ileus. The ileal tumor, measuring 2cm, was detected and resected with regional lymphadenectomy. At that time, a pathologic diagnosis of malignant peripheral nerve sheath tumor was made. The patient, who was not treated with chemotherapy, showed no signs of recurrence. After three years, we detected cervical lymphadenopathy and multiple duodenal masses in the patient in our hospital. Oval to spindle-shaped atypical cells, which resembled ileal tumor cells, infiltrated into the lymph node and duodenum. Immunohistochemical staining of these three lesions revealed positivity of S100 protein and several macrophage-related antigens. Based on the histologic and immunohistochemical analysis, the histopathologic diagnosis of IDCS was confirmed. To our knowledge, five cases of IDCS arising in the intestinal tract have been reported to date, and only one case, treated with both surgery and chemotherapy, led to remission. This is the first case that has a comparatively favorable prognosis without chemotherapy after surgery., (Copyright 2010 Elsevier GmbH. All rights reserved.)

Objective: This study aims to assess the role of three-dimensional single-photon emission computed tomography (3D-SPECT/CT) in sentinel node (SN) identification, and to analyze the impact of such information on estimating metastases to SNs., Background: Nodal status is a key factor for breast cancer. SN biopsy has been established as the alternative to routine axillary dissection these days. We investigated both the anatomical location of SNs demonstrated by our 3D-SPECT/CT system and the correlation to SN positivity., Methods: Two hundred and twenty-three clinically node-negative patients underwent SN biopsy. All of the axillary structures, including SNs, were visualized by a SPECT/CT combined system after subcutaneous injection of (99m)Tc-phytate. By plotting the visualized SNs, the most frequent SN location 'Pedestal area (PA)' was designated., Results: SPECT/CT detected (99m)Tc uptake in 217 cases (97.3%). 3D-SPECT/CT images visualized the accurate location of SNs in each case. In patients whose SNs were histopathologically negative (SN-), 228 (98.3%) SNs were found in the PA, and 4 (1.7%) were in other zones. In those with histopathologically positive SNs (SN+), 65 (78.3%) SNs were in the PA and 18 (21.7%) were outside it. The difference in SN distribution (i.e., in or out of the PA) between SN+ and SN- patients was statistically significant (p<0.001, chi-square test)., Conclusions: SN biopsy navigated by 3D-SPECT/CT can clarify the preoperative anatomical localization of SNs in patients with breast cancer. Atypical distribution of SNs out of the PA may suggest SN positivity, reflecting failure of the lymphatic drainage systems.

Background: This study was performed to clarify the influence of preoperative chemotherapy on liver function and the correlation between histological hepatic injury and the postoperative outcome in patients with colorectal liver metastases who underwent a hepatic resection., Methods: Twenty-seven patients who underwent a hepatic resection for colorectal liver metastases were included. Fifteen patients with initially unresectable colorectal liver metastases who were able to undergo a tumor resection after FOLFOX (oxaliplatin plus fluorouracil and leucovorin, with a mean number of 7.7 cycles) were compared to 12 patients who underwent a hepatectomy with no preoperative chemotherapy. The postoperative mortality, morbidity, changes in liver function tests, and pathology of the resected liver were examined., Results: Preoperative FOLFOX therapy was significantly associated with the macroscopic appearance of oxaliplatin-associated blue liver (p = 0.02), and a tendency toward sinusoidal dilatation (33.3% in the FOLFOX group versus 8.3% in the no-chemotherapy group, p = 0.056). Preoperative liver function tests showed that the albumin and indocyanine green retention rate at 15 min (ICG-R15) test values were significantly worse after FOLFOX therapy; however, intraoperative events, postoperative liver function test values, and morbidity rates were similar in the two groups. There was no postoperative mortality in any of the patients., Conclusions: Although preoperative FOLFOX administration in patients with colorectal liver metastases caused macroscopic blue liver, microscopic sinusoidal dilatation in the liver parenchyma, and a significant decrease in liver function, there was no increase in the morbidity and mortality rates, in comparison to findings in patients without preoperative chemotherapy.

While anti-cancer chemotherapy has improved the survival of patients with hematologic malignancies, it has also exposed such patients to the risk of life-threatening infection due to neutropenia. In intensive chemotherapy for leukemia, invasive aspergillosis resulting in death is infrequently observed. In such cases, aggressive diagnostic and therapeutic intervention is required. Herein, we report a case of Aspergillus liver abscesses in a patient with acute monoblastic leukemia. The patient presented with febrile neutropenia and concomitantly with an elevated serum beta-D: -glucan level during chemotherapy. The abscesses were finally diagnosed by liver biopsy. Although antifungal monotherapy of voriconazole or liposomal amphotericin B, both of which are recommended for invasive aspergillosis, showed a poor response, when combined with micafungin, an echinocandin, both had a highly favorable effect against the infection. Therefore, our clinical experience suggests that the serum test is useful for the rapid diagnosis of invasive aspergillosis, especially in deep tissues, and that combination antifungal therapy with micafungin should be considered when initial monotherapy for fungal infection shows an insufficient effect.

Although numerous macrophages are found in the lesions of Langerhans cell histiocytosis (LCH), their activation phenotypes and their roles in the disease process have not been clarified. Paraffin-embedded LCH samples were examined on immunohistochemistry and it was found that CD163 can be used to distinguish infiltrated macrophages from neoplastic Langerhans cells (LC). The number of CD163-positve macrophages was positively correlated with the number of multinucleated giant cells (MGC), indicating that most MGC are derived from infiltrated macrophages. A significant number of CD163-positive macrophages were positive for interleukin (IL)-10 and phospho-signal transducer and activator of transcription-3 (pSTAT3), an IL-10-induced signal transduction molecule. This indicates that these macrophages are polarized to anti-inflammatory macrophages of M2 phenotype. Tumor-derived macrophage-colony-stimulating factor (M-CSF) was considered to responsible for inducing M2 differentiation of infiltrated macrophages. The number of CD163-positive macrophages in different cases of LCH varied, and interestingly the density of CD163-positive macrophages was inversely correlated with the Ki-67-positivity of LC. Although the underlying mechanism is not fully elucidated, macrophage-derived IL-10 was considered to be involved in the suppression of tumor cell proliferation via activation of STAT3.

Ectopic adrenocorticotropic hormone (ACTH) production by the pancreatic neuroendocrine tumor (p-NET) is relatively rare, and patients with this tumor show poor prognosis. In this study, we present the case of a 64-year-old woman who presented with ectopic ACTH syndrome due to p-NET with multiple liver metastases. Computed tomography revealed that she had multiple masses in the liver and a solid mass in the head of the pancreas. Endocrinological examinations revealed markedly elevated plasma ACTH (735.0 pg/mL) and cortisol (34.7 microg/dL) levels associated with hypokalemia (2.7 mEq/L), diabetes and typical Cushingoid features. Histological examinations by needle biopsy of liver tumors in S5 and S8 indicated metastatic ACTH-producing NET, which was also confirmed by venous sampling. The metastatic live tumor was somatostatin receptor (SSTR)-2a- and SSTR-5-positive as revealed by immunohistochemical staining, and reverse transcription polymerase chain reaction revealed divergent expression patterns of SSTRs, pro-opiomelanocortin, and gastrin mRNA. To avoid complications of hypercortisolemia, metyrapone was first administered to reduce the cortisol levels. After near-normalization of cortisol levels, transarterial chemoembolization and somatostatin analogue treatment were performed. The combination of these treatments effectively decreased ACTH and cortisol levels and also ameliorated hyperglycemia. We have achieved controlled hormone secretion and prevented tumor growth in this patient for more than 20 months, suggesting that highly individualized treatment for NET should be undertaken because of its divergent and heterogeneous characteristics.

Hairy cell leukemia (HCL) is occasionally misdiagnosed as aplastic anemia when only a few leukemic cells are present in the circulation. Here, we describe a patient with HCL who initially presented with pancytopenia and received a diagnosis of aplastic anemia. The patient was treated with immunosuppressive therapy including cyclosporine A and anti-thymocyte globulin (ATG). No blood cell transfusion was required for approximately 3 years after ATG therapy. She was referred to our hospital because of an abdominal mass and requiring periodic blood transfusions. A bone marrow biopsy at this time revealed proliferation of lymphocytes with a fried egg appearance and an increase in reticulin fibers that are typical findings of HCL. It is notable that our patient with a presumably long history of HCL and an increase in marrow reticulin fibers showed good recovery of hematopoiesis after cladribine therapy. Some HCL patients may receive an initial diagnosis of aplastic anemia and may show a good response to ATG masking the underlying HCL.

This study examined the effect of ozagrel, a thromboxane A(2) synthase inhibitor, on the accumulation of leucocytes and chemokine mRNA expression in lungs experimentally injured using oleic acid (OA). OA injection into guinea pigs rapidly increased thromboxane A(2) generation and subsequently increased total protein concentration and the numbers of macrophages and neutrophils in bronchoalveolar lavage fluid and increased monocyte chemoattractant protein-1 and interleukin-8 mRNA expression in the whole lung. Administration of ozagrel prevented these changes associated with OA injection. Ozagrel is a promising drug candidate for preventing acute lung injury.

A 50-year-old female complained of back pain. Computed tomography showed a well-defined spindle-shaped mass 3.4 x 1.0 cm in size in the left paravertebral posterior mediastinum at the Th 3-4 level. The tumor was completely resected via thoracoscopic surgery, which showed no invasion into the surrounding tissue. It consisted of a cyst with a tiny mural solid element. By means of histological and immunohistochemical examinations, we diagnosed the tumor as ependymoma, and the patient remains alive 59 months after resection. As far as we know, 8 reported cases with primary mediastinal ependymoma have been reported. They had the following specific characteristics: (1) All patients were adult females; (2) The tumors were usually located at the paravertebral upper mediastinum; (3) Most of the tumors consisted of cystic and solid elements; (4) The tumors usually made no invasion into the surrounding tissues, though 2 cases had lymph-node metastases.

Background: Although cumulative evidence supports the fact that stromal myofibroblasts promote tumor progression, the influence of myofibroblasts on intrahepatic cholangiocarcinoma (ICC) is unclear. We hypothesized that hepatic stellate (HS) cells can differentiate into myofibroblasts in ICC stroma and that they promote cancer progression. This study aims to: (1) assess the influence of myofibroblasts on the prognosis of ICC, (2) identify HS cells in ICC stroma, and (3) investigate the interaction between HS cells (LI90 and LX-2) and ICC cells (HuCCT-1 and MEC) in vitro., Methods: The association between alpha-smooth muscle actin (alpha-SMA) expression and the prognoses of 46 ICC patients after hepatic resection was evaluated by immunohistochemical analysis. The HS cells in myofibroblasts of ICC were identified (double immunostaining) using antibodies for alpha-SMA, glial fibrillary acidic protein (GFAP), and desmin. The influence of HS cells on the invasion and growth of ICC cells was examined in vitro using a coculture system., Results: Patients with high alpha-SMA expression exhibited the worse outcomes. Multivariate analyses revealed that high alpha-SMA expression (P = 0.0045) and positivity for lymph-node metastasis were independent prognostic factors. Because desmin- or GFAP-positive cells coexpressing alpha-SMA were observed in the ICC samples, they were considered to be derived from the HS cells. On coculturing with HS cells, a remarkable increase was observed in the invasion and growth of the two ICC cell lines., Conclusions: Stromal myofibroblasts may relate to the poor prognoses in ICC patients. HS cells appear to be involved in the progression of ICC.

Presented herein is the second case of sialadenoma papilliferum of the bronchus in a 75-year-old man. The bronchial tumor had an exophytic papillary lesion protruding into the lumen of the ostial region of the right superior lobe bronchus on chest CT and bronchoscopy. Grossly, the resected tumor was pedunculated, 5 x 3 x 3 mm in size and consisted of both an exophytic papillary lesion protruding into the bronchial lumen and a glandular component in the bronchial submucosa. Histologically, the papillary structures were lined by ciliated or non-ciliated columnar epithelium and metaplastic non-keratinizing stratified squamous epithelium. The submucosal glandular components were well circumscribed beneath and in continuity with the papillary lesion. The glandular components of cysts and duct-like structures were lined by a double-layer epithelium composed of luminal cells and basal cells. Sialadenoma papilliferum is a rarely recognized salivary gland tumor, mostly occurring at intraoral mucosal sites including the hard and soft palate and buccal mucosa. There have been sporadic cases of sialadenoma papilliferum of the esophagus, nasopharynx and nasal cavity. To the authors' knowledge only one case of sialadenoma papilliferum of the bronchus has been reported previously.

A 57-year-old woman complained of a huge and rapid growing mass with bleeding in the left breast. Breast imaging (CT and MRI)showed a large, irregular and unevenly enhanced tumor with lymph node swelling in the left axilla. Mastectomy and axillary lymph node dissection were performed for control of bleeding from the tumor in the left breast. Pathological diagnosis was spindle cell carcinoma of the breast with transition from papillotubular carcinoma. Although the patient was treated with adjuvant chemotherapy and trastuzumab according to the treatment guideline for conventional breast cancer, she had an early relapse with mediastinal metastasis and died 9 months after operation. The tumor showed metaplastic change from epithelial tumor to spindle cell carcinoma. Because the epithelial part expressed weakly positive estrogen receptor(ER), progesterone receptor(PgR)-negative and HER2-positive, we used trastuzumab for adjuvant therapy. However, part of the spindle cell tumor mainly showed triple-negative, and ER, PgR and HER2 expression were negative, which might explain her poor prognosis for resistance to trastuzumab.

Purpose: Our purpose was to determine whether the local application of fibroblast growth factor (FGF) 2 accelerates regeneration and remodeling of rotator cuff tendon defects reconstructed with acellular dermal matrix (ADM) grafts in rats., Methods: Thirty adult male Sprague-Dawley rats were divided into equal groups undergoing FGF-treated and FGF-untreated repairs. All rats underwent placement of an ADM graft for the supraspinatus defect (3 x 5 mm). FGF-2 (100 microg/kg) in a fibrin sealant was applied to both shoulders in the FGF-treated group, whereas only fibrin sealant was applied in untreated group. At 2, 6, and 12 weeks after surgery, 5 rats (10 shoulders) in each group were sacrificed for histologic analysis (3 shoulders) and biomechanical testing (7 shoulders). The controls were 5 unoperated rats (3 histologic and 7 biomechanical control specimens)., Results: Unoperated control tendons inserted into the bone by direct insertion; there was a zone of fibrocartilage between the tendon and bone. At 2 weeks, the FGF-treated group had tendon maturing scores similar to those in the untreated group (P > .05). At 6 and 12 weeks, the FGF-treated group had significantly higher scores (P < .05). At 2 weeks, specimens in both the treated and untreated groups exhibited similar strength; the ultimate tensile failure load was 6.0 +/- 4.0 N and 5.8 +/- 2.0 N, respectively (P > .05). At 6 weeks, the FGF-treated specimens were stronger, with an ultimate tensile failure load of 10.2 +/- 3.1 N compared with 7.2 +/- 2.2 N in the untreated group (P = .02). At 12 weeks, the FGF-treated specimens were stronger, with an ultimate tensile failure load of 15.9 +/- 1.6 N compared with 13.2 +/- 2.0 N in the untreated group (P = .0072), and there were no significant differences in strength compared with the controls (17.8 +/- 2.6 N) (P > .05)., Conclusions: The remodeling of ADM grafts placed in rat rotator cuff tendon defects was accelerated by the local administration of FGF-2., Clinical Relevance: The application of FGF-2 may result in improved histologic characteristics and biomechanical strength in ADM graft constructs in humans.

Methods: We investigated the effect of application of fibroblast growth factor (FGF)-2 on the tendon-to-bone remodeling of repaired supraspinatus tendon in rats subjected to bilateral detachment. FGF-2 (100 mg/kg) in a fibrin sealant or sealant alone was applied on the right and left shoulders, respectively. Twelve animals each at 2, 4, and 6 weeks after surgery were sacrificed for histological analysis (n = 5) and biomechanical Q1 testing (n = 7)., Results: Histologically, at 2 weeks, FGF-treated specimens had significantly higher tendon-to-bone insertion maturing scores then untreated specimens (P < .002). At 4 and 6 weeks, the scores of FGF-treated and untreated specimens were similar (P > .05). Biomechanically, FGF-treated specimens were stronger at 2 weeks (P = .001); at 4 and 6 weeks, both specimens exhibited similar strength (P > .05)., Conclusions: The initial tendon-to-bone remodeling was accelerated by a local application of FGF-2. This may represent a clinically important improvement in rotator cuff repair.

Presented herein is the first case of malignant adenomyoepithelioma (malignant AME) of the breast combined with invasive lobular carcinoma (ILC) in a 53-year-old woman. Histologically, the tumor was composed of nodular proliferation of biphasic epithelial and myoepithelial carcinoma, partially surrounded by ILC. Interestingly, ILC metastasized to the axillary lymph nodes, while biphasic epithelial and myoepithelial carcinoma hematogenously metastasized to the lung and the kidney. On immunohistochemistry the biphasic carcinoma consisted of cytokeratin (CK) 8/18-positive/CK5/6-positive/smooth muscle actin (SMA)-negative inner carcinoma cells and CK8/18-positive/CK5/6-positive/SMA-positive outer carcinoma cells. The monophasic ILC cells had a CK8/18-positive/CK5/6-negative/SMA-negative staining pattern. Although it is unclear whether both ILC and biphasic epithelial and myoepithelial carcinoma originated from AME or whether ILC occurred independently of malignant AME, this is an exceptionally rare case, which might give rise to a special consideration of the histogenesis of breast cancer.

Hypothesis: With the acellular dermal matrix (ADM), it may be possible to bridge large rotator cuff tears and induce tendon regeneration., Materials and Methods: A 3 x 5 mm defect of the rotator cuff was created on both shoulders of adult male Sprague-Dawley rats. The graft group (n = 15) underwent reconstruction of the rotator cuff defect with an ADM patch graft; in the defect group (n = 15) no repair was performed. We sacrificed 5 rats from each group at 2, 6, and 12 weeks after surgery and harvested both shoulders; 3 specimens were subjected to histological analysis and the other 7 specimens were used for biomechanical testing. The controls were 5 unoperated rats; they were sacrificed to obtain 3 histologic and 7 biomechanical control shoulder specimens., Results: At each time points, the graft group had significantly higher modified tendon maturing scores than the defect group (p < 0.002); specimens from the graft group demonstrated a greater mean ultimate force to failure than those from the defect group (p < 0.05). Within 12 weeks, the ADM graft was histologically incorporated into a structure resembling control specimen; the mean ultimate force to failure in control was significantly greater than in specimens from both groups (p < 0.01)., Discussion: Although the defect was restored in the defect group, histologically and biomechanically specimens from the defect group were inferior to the graft group., Conclusion: ADM grafts were useful as a scaffold in the reconstruction of large rotator cuff defects in rats., Level of Evidence: Basic science study.

We present the cases of 3 children with huge undifferentiated sarcoma of the liver who were treated with surgical excision including liver transplantation as an option and adjuvant chemotherapy. All 3 patients were males aged 10, 13, and 15 years old. The size of the tumor was 10, 15, and 20 cm in diameter, respectively. The youngest patient is disease free and doing well 43 months after resection. The 13-year-old patient presented with tumor rupture and underwent operation. The primary tumor and the ruptured tissue fragments were removed and he was given postoperative chemotherapy. The patient is disease free and doing well 52 months after surgery. The oldest patient had an unresectable tumor in the hilar region. Preoperative chemotherapy was given but later discontinued owing to severe side effects. He underwent living donor liver transplantation followed by postoperative chemotherapy. The patient had recurrent tumor 24 months after transplantation that was excised at reoperation. He is doing well and is disease free 18 months after the second procedure. Complete removal of the tumor including total hepatectomy and transplantation when indicated and suitable pre- and/or postoperative chemotherapy is an effective treatment for children with undifferentiated sarcoma of the liver.

Metastatic gastric tumors originating from malignant fibrous histiocytoma (MFH) are rare. We herein report the case of a 75-year-old woman who underwent a distal gastrectomy for gastric metastasis of MFH, who was preoperatively diagnosed by an endoscopic ultrasound-guided fine-needle aspiration biopsy.

This report presents a case of multiple gastrointestinal stromal tumors (GIST) with neurofibromatosis type 1 (NF1). A 68-year-old woman was admitted to the hospital because of a tumor close to the head of the pancreas. Imaging studies revealed submucosal tumors of the duodenum. The retroperitoneal tumor was diagnosed before surgery. Besides the main tumor in the duodenum, multiple small submucosal tumors were found in the duodenum and upper part of the jejunum during the operation. All of these tumors were resected. The histological diagnosis of all these tumors was GISTs. These tumors were immunohistochemically positive for KIT, but they demonstrated no mutation in c-kit exons 9, 11, 13, and 17, and platelet-derived growth factor receptor alpha exons 12 and 18. No recurrence occurred for a year after surgery.

Primary squamous cell cancer of the thyroid gland (SCT) is a rare malignant tumour and is associated with a high mortality. A female patient who suffered from primary SCT is described in this report. The cancer was identified with acute painful swelling of the thyroid gland, when the patient was under periodical observation for her chronic thyroiditis at our outpatient's clinic. In spite of the highly malignant potential of the cancer as indicated by histological examinations, including p53 and MIB-1 index analyses, the patient has been successfully treated so far with surgery and radiation therapy, surviving for more than 34 months with no sign of recurrence or metastasis. Early diagnosis and prompt treatment might have been essential for the successful management of this patient. Further observations and investigations are necessary to clarify the mechanisms of the long survival and to find a better treatment for the disease.

Objectives: Although positron emission tomography (PET) using F-fluorodeoxy-glucose (FDG) frequently gives false-negative results for slow-growing tumors, C-acetate (AC)-PET has been reported to be able to detect them. To determine the usefulness of AC-PET for imaging non-small cell lung cancers (NSCLCs), the sensitivity and specificity were compared between the AC-PET and FDG-PET with a multicenter study., Materials and Methods: A total of 284 pulmonary lesions (227 NSCLCs and 57 benign lesions) were examined using both AC-PET and FDG-PET before surgery at seven Japanese institutes. The AC- or FDG-uptake in each lesion were quantitatively measured using the contrast ratio of the standard uptake value between the lesions and the contralateral lung., Results: The sensitivity of AC-PET for diagnosing NSCLC was 0.71, which was significantly higher than the value of 0.57 obtained by FDG-PET (p < 0.001). No significant difference in the specificity was seen between AC- and FDG-PET. For the 146 well-differentiated adenocarcinomas, the sensitivity of AC-PET was 0.62, which was significantly higher than the value of 0.37 obtained by FDG-PET (p < 0.001). Of the 51 moderately- or poorly-differentiated adenocarcinomas and 30 nonadenocarcinomas, there was no significant difference of sensitivity between AC- and FDG-PET., Conclusions: AC-PET could be used in place of FDG-PET for imaging NSCLC, with higher sensitivity for well-differentiated adenocarcinoma compared with FDG-PET.

Background and Purpose: Although the prognostic value of perfusion MR imaging in various gliomas has been investigated, that in high-grade astrocytomas alone has not been fully evaluated. The purpose of this study was to evaluate retrospectively whether the tumor maximum relative cerebral blood volume (rCBV) on pretreatment perfusion MR imaging is of prognostic value in patients with high-grade astrocytoma., Materials and Methods: Between January 1999 and December 2002, 49 patients (30 men, 19 women; age range, 23-76 years) with supratentorial high-grade astrocytoma underwent MR imaging before the inception of treatment. The patient age, sex, symptom duration, neurologic function, mental status, Karnofsky Performance Scale, extent of surgery, histopathologic diagnosis, tumor component enhancement, and maximum rCBV were assessed to identify factors affecting survival. Kaplan-Meier survival curves, the logrank test, and the multivariate Cox proportional hazards model were used to evaluate prognostic factors., Results: The maximum rCBV was significantly higher in the 31 patients with glioblastoma multiforme than in the 18 with anaplastic astrocytoma (P < .03). The 2-year overall survival rate was 67% for 27 patients with a low (< or =2.3) and 9% for 22 patients with a high (>2.3) maximum rCBV value (P < .001). Independent important prognostic factors were the histologic diagnosis (hazard ratio = 9.707; 95% confidence interval (CI), 3.163-29.788), maximum rCBV (4.739; 95% CI, 1.950-11.518), extent of surgery (2.692; 95% CI, 1.196-6.061), and sex (2.632; 95% CI, 1.153-6.010)., Conclusion: The maximum rCBV at pretreatment perfusion MR imaging is a useful clinical prognostic biomarker for survival in patients with high-grade astrocytoma.

Purpose: The aim of this study is to clarify characteristics of invasive breast cancer with expression of Hypoxia-induced factor 1alpha (HIF-1alpha) which is induced by hypoxia and signal transduction of growth factors., Experimental Design: We examined, by immunohistochemical analysis, the expression of HIF-1alpha in normal breast tissue, benign disorders and breast cancer. In invasive breast cancer, we investigated the correlation between expression of HIF-1alpha and clinicopathological and biological factors. We also studied the prognostic value of HIF-1alpha in breast cancer., Results: HIF-1alpha was mainly detected in tumor cell nuclei. In the 171 cases of invasive breast cancer examined, nuclear HIF-1alpha expression was detected in 63 (36.8%) cases. Immunoreactive nuclear HIF-1alpha was correlated with tumor size (p = 0.0013), lymph node metastasis (p = 0.0005), tumor stage (p = 0.0031) and histological grade (p = 0.0074). Elevated HIF-1alpha levels was also associated with hormone receptor negativity (p = 0.0025), HER2 overexpression (p = 0.0053), high Ki67 labeling index (p = 0.0002), increased levels of VEGF (p < 0.0001), COX-2 overexpression (p = 0.0029) and increased nuclear p53 (p = 0.0048). In terms of the possible use of HIF-1alpha as a prognostic indicator, patients who had increased HIF-1alpha levels in their tumor showed shorter disease-free survival (DFS) (p < 0.0001) and overall survival (OS) (p = 0.0002) than those lacking HIF-1alpha in univariate analysis. In multivariate analysis of DFS and OS, HIF-1alpha was identified an independent prognostic factor., Conclusions: These findings suggest that HIF-1alpha was closely linked to an aggressive phenotype in breast cancer. It may be useful to study the expression of HIF-1alpha using immunohistochemical analysis for better understanding of the tumor characteristics of breast cancer.

Background: The mechanisms of generation and progression of multicentric lung adenocarcinoma (AD), bronchioloalveolar carcinoma (BAC), and atypical adenomatous hyperplasia (AAH) in the peripheral lung is not well known. In this study, we analyzed epidermal growth factor receptor (EGFR) mutations in the cases of multicentric AD, BAC, and AAH to reveal the role of EGFR mutation in their generations and progressions., Method: Ninety-seven AAH, BAC, or AD lesions less than 3 cm in size in 26 patients were surgically resected. Of these, EGFR mutations of the nodules with the highest and the second highest grade of histologic malignancy were examined in each patient by using the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp method., Results: EGFR mutations could be examined in 48 nodules in the 26 patients. The EGFR mutations were found more frequently in lesions with higher histologic malignancy, ie, 9 of 10 ADs (90%), 16 of 28 BACs (57%), and one of 10 AAHs (10%). In 22 patients who could be examined of EGFR mutations for the two lesions in each patient, only two patients (9%) had the same mutation patterns between the two lesions, whereas 15 patients (68%) had the different statuses and the remaining five (23%) had no mutations., Conclusion: Our data demonstrated that EGFR mutations seem to contribute to the acquisition of malignant potential in the AAH-AD sequence and occur independently in each lesion and in the cases of multicentric AD, BAC, and AAH.

Background: The destruction of the basement membrane (BM) is the first step in cancer cell invasion and metastasis. Type IV collagen is a major component of the BM, and is composed of six genetically distinct alpha(IV) chains: alpha1(IV) to alpha6(IV). The loss of alpha5/alpha6(IV) chains from the epithelial BM at the early stage of cancer cell invasion has been reported in several cancers. However, the expression of alpha5/alpha6(IV) chains in esophageal squamous cell carcinoma (ESCC) remains unclear., Methods: The expression of alpha(IV) chains in 116 resected ESCC specimens was immunohistochemically examined. The role of alpha6(IV) chain was assessed in ESCC cell lines by short interfering RNA (siRNA)., Results: In intraepithelial carcinoma, the alpha5/alpha6(IV) chains were stained in a continuous linear pattern in the BM. In some cases of ESCC with the invasion beyond the lamina propria, the alpha5/alpha6(IV) chains were lost in the BM zone surrounding the cancer cell nests, but in other cases they remained. In the former, the disease-free survival and overall survival were significantly better than in those with the latter. The down-regulation of alpha6(IV) chain expression by siRNA revealed a slight increase of cancer cell invasiveness., Conclusions: The evaluation of alpha5/alpha6(IV) chains may be a useful marker for determining tumor cell properties, as a prognostic factor, in patients with ESCC.